Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEIHMT-MST1-58Cat.No.:HY-151257CASNo.:2414484-25-4分?式:C??H??N?O?S分?量:438.5作?靶點:Hippo(MST)作?通路:StemCell/Wnt儲存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性IHMT-MST1-58?種有效的、選擇性的STE20-likeprotein1kinase(MST1)抑制劑，具有?服活性，IC50值為23nM。IHMT-MST1-58可?于1型或2型糖尿病的研究。IC50&TargetMST123nM(IC50)體外研究IHMT-MST1-58(compound19)showsgoodactivityagainstMST1withanIC50valueof23nM[1].IHMT-MST1-58(1μM)displaysstronginhibitoryactivityagainstMST1(IC50=23nM),weakactivityagainstMST2(IC50=652nM),butnoactivityagainstNEK3evenat10μM(IC50>10μM)[1].IHMT-MST1-58(1μM)showsstrongbindingaffinitytoMST1andweakbindingaffinitytoMST2withKdvaluesof240nMand2.7μM[1].IHMT-MST1-58(0.1-10μM;1-2h)inhibitsthephosphorylationofMST1invitro[1].IHMT-MST1-58(0.03,0.1and0.3μM;48h)exhibitsasignificantprotectiveeffectofβcellsfromthedamagecausedbyinflammatorycytokines[1].WesternBlotAnalysis[1]CellLine:HepG2livercells,RAW264.7,RPE1andHL7702cells;INS-1andRIN-m5FcelllinesConcentration:0-10μMIncubationTime:2h(HepG2livercells,RAW264.7,RPE1,andHL7702cells)Result:InhibitedtheH2O2-stimulatedMOB1phosphorylationandMST1/2autophosphorylation1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEinadose-dependentmannerinallfourcelllines.InhibitedthephosphorylationofLATS1(T1079)andYAP(S127)inHepG2cells.ShowedstronginhibitionofMST1phosphorylationanditsdownstreamMOB1autophosphorylationinadose-dependentmannerinbothcelllines.體內(nèi)研究IHMT-MST1-58(compound19)(p.o,50mg/kg/day,QD)combinationwithmetforminledtothedeclineoffastingbloodglucose,showprotectiveeffectofβcellsanddecreasethehemoglobinA1clevelintheSTZ-inducedT1D/T2Dmousemodels[1].PharmacokineticParametersofIHMT-MST1-58indifferentspecies(i.v.orp.o;1mg/kg,5mg/kgand10mg/kg)[1].miceratsbeagledogsparameteri.v.(1mg/kg)p.o.(10mg/kg)i.v.(1mg/kg)p.o.(10mg/kg)i.v.(1mg/kg)p.o.(10mg/kg)AUC0-t(ng/mL*h)501.155832553±155.14858±2648764.5±82.94939±1067t1/2(h)1.71.813.51±0.343.03±0.26.47±0.715.79±1.09Cmax/F(ng/mL)12401922944.0±219.11717±276466.7±45.21113±417F(%)-110.8-73.3±40.1-106.5±20.9AnimalModel:mice[1]Dosage:50mg/kgAdministration:oral,singleResult:parameterplasmapancreasCmax(ng/mL)3990±39012216±1509AUC0-t(ng/mL*h)13621±212751394±10098Cl(mL/h/kg)3734±641996±189AnimalModel:T1DmousemodelsandT2Dmousemodels[1]Dosage:50mg/kgAdministration:p.o,50mg/kg/day,QDResult:DecreasedtheFBGlevel,improvedthefoodintakeandwaterconsumption,hadlowHbA1candagoodantidiabeticeffect,improvedthehistologicalstructureoftheislet.AnimalModel:mice,SpragueDawleyrats,andbeagledogs[1]Dosage:1mg/kg,5mg/kgand10mg/kgAdministration:intravenousinjectionandoraladministrationResult:Displayedacceptablepharmacokineticpropertiesindifferentspecies.REFERENCES[1].YunWu,etal.DiscoveryofIHMT-MST1-58asaNovel,Potent,andSelectiveMST1InhibitorfortheTreatmentofType1/2Diabetes.J2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMedChem.2022Sep8;65(17):11818-11839McePdfHeightCaution:Producthasnotbeenf